Tick galactosyltransferases are involved in alpha-Gal synthesis and play a role during Anaplasma phagocytophilum infection and Ixodes scapularis tick vector development

Alejandro Cabezas-Cruz (1) , Pedro J. Espinosa (2) , Pilar Alberdi (2) , Ladislav Simo (1) , James J. Valdes (3, 4, 5) , Lourdes Maeteos Hernandez (1, 2) , Marinela Contreras (2) , Margarita Villar Rayo (2) , Jose de La Fuente (2, 6)

1 BIPAR - Biologie moléculaire et immunologie parasitaires et fongiques
2 SaBio
3 Faculty of Science
4 CAS - Czech Academy of Sciences [Prague]
5 Veterinary Research Institute
6 Department of Veterinary Pathobiology, Center for Veterinary Health Sciences

The carbohydrate Gal alpha 1-3Gal beta 1-(3)4GlcNAc-R (alpha-Gal) is produced in all mammals except for humans, apes and old world monkeys that lost the ability to synthetize this carbohydrate. Therefore, humans can produce high antibody titers against alpha-Gal. Anti-alpha-Gal IgE antibodies have been associated with tick-induced allergy (i.e. alpha-Gal syndrome) and anti-alpha-Gal IgG/IgM antibodies may be involved in protection against malaria, leishmaniasis and Chagas disease. The alpha-Gal on tick salivary proteins plays an important role in the etiology of the alpha-Gal syndrome. However, whether ticks are able to produce endogenous alpha-Gal remains currently unknown. In this study, the Ixodes scapularis genome was searched for galactosyltransferases and three genes were identified as potentially involved in the synthesis of alpha-Gal. Heterologous gene expression in alpha-Gal-negative cells and gene knockdown in ticks confirmed that these genes were involved in alpha-Gal synthesis and are essential for tick feeding. Furthermore, these genes were shown to play an important role in tick-pathogen interactions. Results suggested that tick cells increased alpha-Gal levels in response to Anaplasma phagocytophilum infection to control bacterial infection. These results provided the molecular basis of endogenous alpha-Gal production in ticks and suggested that tick galactosyltransferases are involved in vector development, tick-pathogen interactions and possibly the etiology of alpha-Gal syndrome in humans.

Domaines: Sciences du Vivant [q-bio]

Alejandro Cabezas-Cruz, Pedro J. Espinosa, Pilar Alberdi, Ladislav Simo, James J. Valdes, et al.. Tick galactosyltransferases are involved in alpha-Gal synthesis and play a role during Anaplasma phagocytophilum infection and Ixodes scapularis tick vector development. Scientific Reports, 2018, 8, ⟨10.1038/s41598-018-32664-z⟩. ⟨hal-02624085⟩